Abstract TP26: Changes In Health-seeking Behavior Of Stroke Patients During Three Covid-19 Outbreaks: Data From The Korean Stroke Registry

Stroke, Volume 53, Issue Suppl_1, Page ATP26-ATP26, February 1, 2022. Introduction:The coronavirus disease 2019 (COVID-19) pandemic has changed the medical use of stroke patients. This study evaluated the health-seeking behavior of stroke patients and changes in stroke care services at the time of three domestic COVID-19 outbreaks in Korea using the Korean Stroke Registry (KSR) data.Methods:We reviewed data from patients with acute stroke and transient ischemic attack (TIA) from Jan 2019 to May 2021. There were three domestic COVID-19 outbreaks (1st: Feb to Mar 2020, 2nd Aug to Sep 2020, 3rd Nov 2020 to Jan 2021). Outcomes included patient characteristics, times from stroke onset to hospital arrival, and in-hospital stroke pathways.Results:The study included 34,271 patients who visited hospitals that contribute to the KSR. In the first outbreak, in Daegu city (the main epicenter), the number of patients decreased by two-thirds compared to the pre-COVID period, and the number of TIA patients was particularly decreased (9.97% to 2.91%). Unlike other regions, the median onset-to-door time increased significantly in the epicenter (361 min vs. 526.5 min, p=0.016), and longer times were common for patients with mild symptoms and who were in their 60s or 70s. The median onset-to-door time increased in the epicenter during the second outbreak, but it was not statistically significant. At the third outbreak, the median onset-to-door time was reduced even in the epicenter compared to the previous one. The number of patients decreased with each outbreak compared to the previous one, but the decrease gradually became smaller.Conclusions:Korean stroke patients in a COVID-19 outbreak region showed clear changes in health-seeking behaviors and showed a pattern of adaptation to the COVID-19 environment. There is a need for continued attention to an appropriate triage system and public education on the importance of early treatment during the COVID-19 pandemic.

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Febbraio 2022

Abstract TMP21: Impact Of COVID-19 State-level Hospital Capacity On Overall Stroke Mortality In 2020 In The United States

Stroke, Volume 53, Issue Suppl_1, Page ATMP21-ATMP21, February 1, 2022. Background:Although hospital admissions for stroke declined in 2020 during the COVID-19 pandemic, patients with comorbid COVID-19 and stroke had increased mortality. We explored stroke mortality in 2020 and its association with COVID-19 prevalence and state-level hospital capacities.Methods:We analyzed CDC National Vital Statistics System and COVID Data Tracker data from 2017-2020. The primary outcome was age-adjusted stroke (ischemic and hemorrhagic) mortality rate per 100,000. The secondary outcome was % change in state-level stroke mortality rates in 2020 (vs. 2017-19); we report its correlation with state-level 1) prevalence of confirmed COVID-19 infections by 12/31/2021, 2) total COVID mortality by 12/31/20, and the 2020 average state-level % of 3) hospital and 4) ICU beds occupied by COVID-19 patients.Results:Figure 1A shows the typical seasonal decline in stroke mortality in quarters 2/3 was attenuated in 2020. The % change in state-level stroke mortality in 2020 (Figure 1B) was not correlated with prevalence of COVID-19 infection (rho=0.05, p=0.74), mortality (rho=0.10, p=0.49), or the % of ICU beds occupied by COVID-19 patients (rho=0.24, p=0.09). There was a correlation with % of hospital beds occupied by COVID-19 patients (rho=0.35, p=0.01) (Figure 2).Conclusion:Overall stroke mortality increased in 2020, particularly in Q2/3, the early-to-mid phase of the COVID-19 pandemic. At the state level, the average % of all hospital beds occupied by COVID-19 patients in 2020 was the only COVID-19 metric associated with change in stroke mortality. Future work should determine if this association was due to decreased hospital capacity to deliver standard stroke care.

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Febbraio 2022

Abstract TP167: Unanticipated Platelet Function Fluctuations Occur During The First 8 Hours After Neurointerventional Procedures In Patients Receiving Dual Anti-platelet Therapy

Stroke, Volume 53, Issue Suppl_1, Page ATP167-ATP167, February 1, 2022. Antiplatelet agents are administered before and after neuroendovascular surgery to minimize implant-associated thromboembolic events. Dual antiplatelet therapy (DAPT) uses aspirin plus P2Y12 receptor inhibitors: clopidogrel, ticagrelor, or prasugrel. Effects are quantified in P2Y12 reactivity units (PRU) and aspirin reactivity units (ARU) by the point-of-care assay, Accumetrics VerifyNow. We hypothesized that intraoperative events such as anesthesia may affect platelet inhibition, increasing the risk of unanticipated ischemic events in the early postoperative period.This retrospective study was approved by the institutional review board. 50 patients who underwent Verify Now testing preoperatively and within 12 hours postoperatively after placement of cervical or intracranial stents at a single institution (January 1, 2018 – May 25, 2021) were included. PRU values > 194 and ARU values > 550 were considered subtherapeutic. Anesthetic agents, heparin dosage, clopidogrel responsiveness, platelet count, liver function, procedure type and length, NIH stroke scale scores, and demographics were compared to perioperative platelet inhibition values.Our results indicate that P2Y12 inhibition is likely affected by intraoperative events. Approximately 25% of patients exhibited marginal (170-193) or subtherapeutic ( > 194) PRU values during the first 8 hours following neuroendovascular procedures. The greatest variation occurred in the ticagrelor group (PRU median change 84) and was more likely to occur with reduced doses of both ticagrelor and clopidogrel. A single prasugrel patient (clopidogrel non-responder) exhibited the greatest absolute change (PRU 156 – > 316). ARU variations were less pronounced suggesting that perioperative aspirin platelet inhibition is more resilient.In conclusion, patients undergoing elective neuroendovascular procedures may be at risk for thromboembolic ischemic complications during the first 8 hours postoperatively due to shifts in P2Y12 mediated platelet inhibition. ARU values were less effected, supporting the use of DAPT as an ongoing clinical standard of care.

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Febbraio 2022

Abstract WMP1: Results From A Phase 2a Study Of TMS-007, An SMTP Family Anti-inflammatory Prothrombolytic, On Patients With Acute Ischemic Stroke Up To 12 Hours After Onset

Stroke, Volume 53, Issue Suppl_1, Page AWMP1-AWMP1, February 1, 2022. Approved thrombolytic agents are limited in their use for the treatment of acute ischemic stroke (AIS) due to their benefit-risk profile beyond 4.5 h since last known normal (LKN). TMS-007 is a small molecule, SMTP family member with a novel mode of action: promotion of plasminogen-fibrin binding to enhance physiological thrombolysis while inhibiting inflammation at the site of thrombosis. TMS-007 may extend the treatment time window based on nonclinical pharmacological evidence. We evaluated TMS-007 in a randomized, placebo-controlled, double-blind, dose-escalation phase 2a study. TMS-007 or placebo was administered as a single intravenous infusion at a dose of 1, 3, or 6 mg/kg to AIS patients who were ineligible for t-PA or thrombectomy within 12 h of LKN. The number of patients allocated to placebo and TMS-007 at doses 1, 3, and 6 mg/kg were 38, 6, 18, and 28, respectively. The combined TMS-007 dosing group (Group T; n = 52) was compared with placebo group (Group P; n = 38). The average age was ~72 years old and time since LKN to treatment was ~9 h in both groups (not significantly different). The incidence of symptomatic intracranial hemorrhage (ICH) with worsening NIHSS score of

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Febbraio 2022

Abstract 53: Covid-19 Spike-protein Causes Cerebrovascular Rarefaction And Deteriorates Cognitive Functions In A Mouse Model Of Humanized ACE2

Stroke, Volume 53, Issue Suppl_1, Page A53-A53, February 1, 2022. COVID-19 pandemic has affected our health and economy. Clinical trials confirmed multiple neurological symptoms due to COVID-19, ranging from headaches, insomnia to stroke, and encephalopathy. More studies are required to unravel the cellular and molecular mechanisms to find a cure for these neurological symptoms. Here, we investigate the effect of COVID-19 spike protein (S-protein) on the cerebrovasculature and cognitive functions in two mouse models that express humanized ACE-2 (h ACE2), a receptor essential for cellular infection and COVID-19 internalization. We hypothesize that COVID-19 S-protein causes cognitive dysfunction via the deterioration of cerebrovascular functions.Methods:S-protein was either injected intravenously or directly into the hippocampus of K-18 (h ACE2 in epithelial cells) or global h-ACE2 knock-in (h ACE2 KI) mice or wild-type mice. Cognitive functions were assessed by Y-maze and Barnes maze. Cerebrovascular density was determined using confocal 3-D image reconstruction. Human brain microvascular endothelial cells (HBMVEC) were treated with S-protein and assessed for apoptosis and inflammatory markers using immunoblotting and RT-PCR. K-18 and h-ACE2 KI mice received intraocular injections of S-protein; retinas were evaluated for vascular cell death and inflammation.Results:S-protein injections caused significant deterioration in memory and learning function of K-18 and h-ACE2 KI mice but not in the wild-type mice (P

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Febbraio 2022

Abstract WP28: Thromboembolic Clot Perviousness In Covid-19: A Case-control Study

Stroke, Volume 53, Issue Suppl_1, Page AWP28-AWP28, February 1, 2022. Background:Large vessel occlusion (LVO) is the most common stroke subtype for those patient’s presenting with COVID-19. Clot perviousness, or a clot’s permeability to iodinated contrast, provides insight to an individual’s responsiveness of hyperacute revascularization, clot origin and functional post-stroke outcomes. We aimed to calculate LVO perviousness for those with and without COVID-19 and its association with revascularization and outcomes.Methods:This is a retrospective case-control study for individuals presenting with middle cerebral artery (MCA) LVO with and without COVID-19 positivity. Clot perviousness was calculated by a blinded experienced neuroradiologist. Perviousness scores were compared with demographic and comorbidity information as well as revascularization and functional outcomes.Results:18 individuals with a MCA LVO (9 COVID-19 infected) were included. Those with COVID-19 were significantly more likely to have diabetes mellitus [67% (6/9) versus 11% (1/9),p= 0.05] and hypertension [89% (8/9) versus 22% (2/9),p= 0.02]. Clot perviousness trended lower in the COVID-19 group [11.0 (8.2 – 26.4) versus 31.7 (30.4 – 39.2), p = 0.10]. Those with COVID-19 infection tended to have a lower clot pervious score, [22% (2/9) versus 78% (7/9), p =0.057]. The majority of those presenting with COVID-19 died during the hospitalization.Conclusions:Our data suggests for those with COVID-19 and MCA LVO, clots tended to be more impermeable to iodinated contrast. This finding may be due to the underlying coagulopathy of COVID-19, namely alternations in fibrin homeostasis.

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Febbraio 2022

Abstract TMP23: Impact Of Covid-19 On Number Of Acute Stroke Patients In Japan: A Nationwide Survey In Primary Stroke Centers

Stroke, Volume 53, Issue Suppl_1, Page ATMP23-ATMP23, February 1, 2022. Background and Purpose:We sought to investigate the impact of COVID-19 pandemic on number of acute stroke patients admitted to Japanese primary stroke centers (PSCs).Methods:The Japan Stroke Society and the MHLW registry of mechanical thrombectomy for acute ischemic stroke conducted a national annual survey of hospitalization volumes for acute ischemic stroke, intracranial cerebral hemorrhage, and subarachnoid hemorrhage in PSCs. Number of acute stroke patients was defined as sum of three stroke subtypes admitted within 7 days after the onset. Monthly acute stroke volumes were compared between 2019 and 2020, among COVID-19 waves, and regional infectious rates.Results:The stroke volume data was completed in 530 PSCs. The annual acute stroke volume was declined 2.5% from 179,893 in 2019 to 174,385 in 2020. Number of acute stoke patients was declined during COVID-19 expanding periods (1stwave, Mar-May; 2ndwave Jul-Aug; 3rdwave Nov-Dec), whereas it was increased in the other months. The mean decline rate of stroke volumes from 2019 to 2020 was greater in 125 PSCs located in prefectures with high estimated SARS-CoV 2 infected rate (more than 2,300 per million people) than in 405 PSCs of the other regions (-4.6±15.4% vs -0.1±20.0%, P=0.008), especially during COVID-19 expanding periods (-8.2±17.9% vs -3.1±21.3%, P=0.009).Conclusions:Acute stroke volumes were declined in 2020 from 2019 in Japanese PSCs, especially during COVID-19 expanding periods and in highly infected regions. The overwhelmed health care system and infection control practices may have associated with decline of number of acute stroke patients during COVID-19 pandemic.

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Febbraio 2022

Abstract WP26: Covid Pandemic Versus Pre-pandemic Care Of Stroke Patients Within The Florida Stroke Registry

Stroke, Volume 53, Issue Suppl_1, Page AWP26-AWP26, February 1, 2022. Background:The coronavirus 2019 (COVID-19) pandemic has affected all aspects of stroke care delivery and resource allocation. We sought to study this effect utilizing the Florida Stroke Registry (FSR), which collects data from hospitals in large metropolitan cities and small communities, each facing pandemic peaks at different timepoints and within various healthcare system organizations.Methods:From March 2019 to March 2021, the FSR identified 82,899 patients with the final diagnosis of ischemic stroke and TIA. Stroke care metrics were compared in patients enrolled during the COVID-19 pandemic (March 2020 to February 2021) to those enrolled in the immediate pre-pandemic year. These metrics included utilization of intravenous thrombolytic (IVT), Endovascular therapy (EVT), Door-To-Needle time (DTN), Door-To-Puncture time (DTP), Door-To-Computed Tomography time (DTCT) and overall Defect-Free Care (DFC).Results:Pre-pandemic patients (n= 41,929, 49.0% female, mean age 70.1 ± 14.6 years, 64.3% white, 20.4% black, 15.3% Hispanic) had similar demographics to pandemic patients (48.8% female, mean age 69.9 ± 14.4 years, 65.4% white, 19.9% black, 14.7% Hispanic). Pandemic stroke patients had more severe presentations (median NIHSS 3 [IQR 8] vs 3 [7], p < .0001), longer onset-to-arrival time (242 [677] vs 229 [654] minutes, p = 0.002), and were more likely to arrive via emergency medical services (62.3% vs. 60.8%, p < .0001) than pre-pandemic stroke patients. Although both groups received IVT equally (13.4% vs. 13.5%, p = 0.67), pandemic stroke patients were more likely to receive EVT (7.0% vs. 6.5%, p = 0.005) and had longer DTP (84 [60] vs. 81 [64] minutes, p = 0.01), shorter DTCT (22 [52] vs 23 [56] minutes, p = 0.01) and similar DTN (36 [22] vs. 37 [22] minutes, p = 0.05) times, with an increased DFC rate of 2.2% (86.6% vs. 84.4%, p < .0001).Conclusions:In this large registry based study, we found that compared to pre-pandemic care, ischemic stroke patients treated during the COVID19 pandemic presented sicker and later to the hospital and were more likely to receive EVT, but had longer door-to-puncture times. Despite many healthcare delivery challenges imposed by COVID19, Florida hospitals within the FSR maintained high quality of stroke care overall.

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Febbraio 2022

Abstract TP22: Coagulation Markers And Stroke Severity In Covid-19 Associated Acute Ischemic Stroke

Stroke, Volume 53, Issue Suppl_1, Page ATP22-ATP22, February 1, 2022. Background:COVID-19 is thought to induce a pro-thrombotic state, which might increase stroke risk. The purpose of this project is to assess stroke severity, type and coagulation markers such as D-dimer, fibrinogen, and CRP in patients with acute ischemic stroke (AIS) and COVID-19, compared to a control group of AIS without COVID-19.Methods:We captured discharge diagnosis of all patients at our medical center with AIS and COVID based on their discharge ICD-10 coding between June 2020 and May 2021; and identified AIS without COVID matched for age, sex, race, and ethnicity. Group 1 was AIS with COVID-19, Group 2 matched (3:1) AIS without COVID-19. We compared baseline demographics, NIHSS, D-dimer, fibrinogen, CRP, presence of large vessel occlusion (LVO) in COVID-19 AIS vs non-COVID-19 AIS. We used a T test to compare parametric and Mann Whitney U for non-parametric values.Results:In total 23 (of 397 total AIS) patients were in Group 1; 69 in Group 2. D-dimer levels (mean) were 3237.3 in Group 1, and 2706.8 in Group 2 (NS), Fibrinogen 464.4 and 379.8 (NS), CRP 7.9 and 9.4 (NS). Median NIHSS was 21 versus 5 (p=0.003). LVO was present in 17 patients in Group 1 (73%) and 23 (33%) in Group 2 (NS). In total, only 5.8% (23 of 397) of all AIS in our data had Covid-19 infection.Conclusion:COVID in stroke was an infrequent finding in our sample (5.8%). Patients with COVID and stroke had higher initial stroke severity, but did not differ in coagulation values. Weather coagulation markers can help distinguish patients with COVID related stroke will require subsequent studies. We need additional data before treatment recommendations specific to stroke in COVID can be made.

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Febbraio 2022